Venetoclax in Combination With ASTX727 for the Treatment of Treatment-Naive High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Key claim: A phase I/II trial is evaluating the safety, optimal dosing, and efficacy of venetoclax combined with oral cedazuridine/decitabine (ASTX727) in treatment-naive patients with high-risk MDS or CMML.
Abstract
This phase I/II trial studies the side effects and best dose of venetoclax in combination with cedazuridine and decitabine (ASTX727) in treating patients with high risk myelodysplastic syndrome or chronic myelomonocytic leukemia who have not received prior treatment (treatment-naive). Chemotherapy drugs, such as venetoclax, cedazuridine, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Why this matters
Treatment-naive high-risk CMML and MDS/MPN overlap disease have historically been managed with single-agent HMA backbones extrapolated from MDS, and this phase I/II trial of venetoclax + ASTX727 is one of the first prospective evaluations of an oral HMA + BCL-2 doublet in the frontline setting for these subtypes. It complements the parallel ASTX727 ± venetoclax randomization (CMML/MDS-MPN with excess blasts) and the AVENHIR (aza+ven) effort by specifically anchoring the combination as upfront therapy, helping define whether BCL-2 inhibition adds value before HMA failure in this defined population.